Sleep is one of the greatest scientific enigmas. The average human will spend 27 years in this state and most will die during it, yet what sleep does for the brain, individual neurons, or glia is not defined on any level. It is unlikely that we will ever understand how the brain works until our understanding of the molecular regulation of sleep improves. Nevertheless, most people intuitively recognize that sleep increases after sleep deprivation or during infection. Further, there is much evidence that those sleep responses and physiological sleep are regulated in part by humoral mechanisms. The investigators hypothesize that tumor necrosis factor (TNFalpha) is one of the key substances in sleep regulation. This hypothesis is based on evidence showing: 1) TNFalpha induces sleep; 2) inhibition of TNFalpha inhibits sleep and sleep induced by sleep deprivation or bacterial products; 3) TNF production is affected by sleep; and 4) TNFalpha and TNF receptors are in brain. To investigate the hypothesis the investigators will use TNF 55 kD receptor knockout mice to identify the type of TNF receptor involved in sleep and determine the role that TNF plays in responses to sleep deprivation and bacterial products (Specific Aim #1). Second, they will determine if TNFalpha mRNA or TNF 55kD receptor mRNA or TNFalpha varies in brain across the day or after sleep deprivation using RTPCR, bioassays, and ELISA methods (Specific Aim #3). Preliminary data for all three specific aims demonstrate the feasibility of the proposed work. Anticipated results aim to provide molecular-mechanistic advances to understanding sleep regulation as well as aid our general understanding of cytokine regulation in the brain.
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| Ingiosi, Ashley M; Opp, Mark R; Krueger, James M (2013) Sleep and immune function: glial contributions and consequences of aging. Curr Opin Neurobiol 23:806-11 |
| Krueger, James M (2012) TRANSLATION OF BRAIN ACTIVITY INTO SLEEP. Hirosaki Igaku 63:S1-S16 |
| Hodgson, Nicole R; Bohnet, Stewart G; Majde, Jeannine A et al. (2012) Influenza virus pathophysiology and brain invasion in mice with functional and dysfunctional Mx1 genes. Brain Behav Immun 26:83-9 |
| Jewett, Kathryn A; Krueger, James M (2012) Humoral sleep regulation; interleukin-1 and tumor necrosis factor. Vitam Horm 89:241-57 |
| Davis, Christopher J; Krueger, James M (2012) Sleep and Cytokines. Sleep Med Clin 7:517-527 |
| Davis, Christopher J; Clinton, James M; Krueger, James M (2012) MicroRNA 138, let-7b, and 125a inhibitors differentially alter sleep and EEG delta-wave activity in rats. J Appl Physiol 113:1756-62 |
| Taishi, Ping; Davis, Christopher J; Bayomy, Omar et al. (2012) Brain-specific interleukin-1 receptor accessory protein in sleep regulation. J Appl Physiol 112:1015-22 |
| Zielinski, Mark R; Taishi, Ping; Clinton, James M et al. (2012) 5'-Ectonucleotidase-knockout mice lack non-REM sleep responses to sleep deprivation. Eur J Neurosci 35:1789-98 |
| Krueger, James M; Tononi, Giulio (2011) Local use-dependent sleep; synthesis of the new paradigm. Curr Top Med Chem 11:2490-2 |
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